We are studying the molecular mechanisms involved in age-dependent thymic involution and T-cell aging. We have demonstrated that expression of beta-catenin in thymocytes in CAT-Tg mice results in accelerated age-dependent thymic involution and aging. Recent analysis demonstrated that expression of beta-catenin inhibits proliferation of developing thymocytes, causes DNA damage,induces oncogene-induced-senescence (OIS) and p53-dependent apoptosis. We believe that this may be a reason why the expression of the powerful oncogene, beta-catenin, does not result in thymic tumors but causes thymic involution. With regard to the observation that expression of beta catenin accelerated thymic involution, we plan to examine if DNA damage, namely OIS and p53-dependent apoptosis, are features of normal aging in wild type mice.